The etiology of breast cancer in younger women (diagnosed < 50 years of age) is poorly understood and understudied. These cancers have a higher prevalence of more aggressive, hormone receptor negative tumors and are associated with poorer prognosis. The incidence rate among women through age 40 years is higher among Black vs. White women, but risk appears to be increasing among White women in the United States. Young Black women also have a higher prevalence of more aggressive, hormone receptor negative tumors. Recent evidence suggests this may also be true for women of lower socioeconomic status (SES). Potentially modifiable risk factors related to energy balance over the life course (e.g. growth patterns, pubertal maturation, adiposity, insulin resistance, diet and physical activity) have been implicated in the etiology of breast cancer in younger women. The objectives of this study are to investigate, in a socioeconomically diverse population of Black and White women, whether life course (in utero/perinatal, childhood, adolescent, and adult) energy balance factors, or polymorphic variation in candidate genes in energy balance pathways, are associated with breast cancer risk overall and by tumor subtype. Specific Aims: Among Black and White women < 50 years, we propose: 1) To investigate the association between adult energy balance factors-general (subcutaneous) adiposity, central (visceral) adiposity, serum adipokine biomarkers, an insulin resistance related diet pattern, and physical activity-with breast cancer risk; (2) To examine the association between early life energy balance factors-growth, adiposity, and onset of menses-with breast cancer risk; and (3) To study joint associations between life course energy balance factors-aforementioned adult and early life factors-with breast cancer risk. All associations will be studied, (a) by race (Black/White) and SES, (b) jointly with candidate genes in the energy balance pathway (based on function and genome wide association studies), and (c) for overall breast cancer and by tumor subtype (basal-like, HER2+/estrogen receptor (ER)-, Luminal A, and Luminal B). Methods: We propose to conduct a population-based case control study of 2,000 incident in situ and invasive breast cancer cases, diagnosed from 2011 to 2014, in Black (n=1,000) and White (n=1,000) women aged < 50 years residing in Metropolitan Detroit and Los Angeles County SEER areas, and a population-based sample of 2,000 control women frequency-matched on age, race and SEER area. We will collect anthropometric measurements, blood, photographs, questionnaire data on life course energy balance and other known risk factors, and tumor tissue. Significance: Our proposed study will, (1) provide insight into potentially modifiable risk factors for breast cancer in younger women, (2) examine risk factors for specific breast tumor subtypes, including the aggressive basal-like/'triple negative' tumors, (3) be the largest study of breast cancer in younger African American women, (4) have the ability to investigate the joint effect of race and SES, and (5) create a bio-repository of blood, tumor tissue microarrays and DNA for current and future study. PUBLIC HEALTH RELEVANCE Breast cancer (BC) in younger women has a greater prevalence of tumors with poor prognosis and is most common in African American women under 40 years of age. Little research has been conducted on causes of BC in young women, particularly by molecular tumor subtypes, but energy balance factors over the life course (growth patterns, onset of menses, body size, physical activity, diet and related genes) have been implicated. This project - the largest study to date of BC in young African American women - will integrate information over the life course to investigate these risk factors overall and by molecular tumor subtypes to lay the foundation for further research, identify populations at highest risk and determine opportunities for modifiable intervention and prevention.